Common variable immunodeficiency (CVID) is the most frequently diagnosed primary immune deficiency in adults. It leaves the body unable to produce enough protective antibodies, making people highly susceptible to repeated infections, particularly in the lungs, sinuses, and gut. CVID affects roughly 1 to 4 people per 100,000, depending on the country, and it often takes years to identify. The median delay between first symptoms and diagnosis is about 7 years, with most people developing symptoms around age 32 but not receiving a diagnosis until around age 40.
How CVID Affects the Immune System
Your immune system normally produces proteins called immunoglobulins (antibodies) that recognize and neutralize bacteria, viruses, and other threats. In CVID, the immune system fails to make adequate amounts of these antibodies, particularly IgG, the most abundant type in the bloodstream. Levels of IgA and IgM, two other antibody classes, are often low as well.
The problem traces back to B cells, the white blood cells responsible for manufacturing antibodies. In people with CVID, B cells don’t mature properly or don’t develop into the memory cells that provide lasting immunity after infections or vaccinations. This means that even after getting a vaccine, your body may not build or maintain a protective response.
What Causes It
The exact cause of CVID remains unknown in most cases. A genetic component clearly exists, but researchers have only pinpointed specific mutations in a fraction of patients. The most commonly identified are mutations in a receptor called TACI, found in roughly 8% to 10% of people with CVID. Other known mutations affect proteins involved in B cell signaling and survival, including CD19, CD81, CD20, CD21, and BAFF. For the majority of patients, though, no single gene explains the condition, and it likely results from a combination of genetic and environmental factors.
CVID can run in families, but it also appears sporadically with no family history. It affects men and women roughly equally.
Symptoms and Warning Signs
The hallmark of CVID is recurrent infections, especially bacterial infections in the respiratory tract. Frequent sinus infections, bronchitis, ear infections, and pneumonia that keep coming back or don’t fully resolve with antibiotics are the most common early signs. Some people also experience chronic diarrhea, unexplained weight loss, or recurrent stomach infections.
What makes CVID tricky to spot is that each individual infection looks ordinary. It’s the pattern that’s abnormal. A person might see different doctors for each episode, and no single provider connects the dots. This is a major reason the diagnostic delay averages 7 years. The longer CVID goes unrecognized, the more damage repeated infections can do, particularly to the lungs. Bronchiectasis, a permanent widening and scarring of the airways from repeated lung infections, is one of the most serious consequences of delayed diagnosis.
How CVID Is Diagnosed
Diagnosis starts with blood tests measuring immunoglobulin levels. For adults, an IgG level below 5 g/L is a key threshold, along with reduced IgA or IgM. But low antibody levels alone aren’t enough. To confirm CVID, doctors also need to rule out other causes of low immunoglobulins (certain medications, protein loss through the kidneys or gut, blood cancers) and demonstrate that the immune system fails to respond properly to vaccines.
This vaccine challenge test is a critical part of diagnosis. You receive a pneumococcal vaccine, and your blood is tested four to six weeks later to see whether your body produced protective antibodies. For adults aged 6 to 65, a normal response means developing protective levels against at least 70% of the bacterial strains in the vaccine. People with CVID typically fall well short of this. The most severely affected produce protective antibodies against two or fewer strains, and even those responses tend to be weak.
Patients must also be older than 4 years at diagnosis, since the immune system in younger children is still developing and low antibody levels may be temporary.
Autoimmune Complications
CVID isn’t just about fighting off infections. The same immune dysfunction that leaves you vulnerable to bacteria can also cause the immune system to attack your own body. Autoimmune complications affect an estimated 20% to 40% of people with CVID, depending on the study.
The most common autoimmune problem is immune thrombocytopenia, where the body destroys its own platelets (the cells responsible for blood clotting). This affects roughly 7% to 14% of CVID patients and can cause easy bruising, bleeding gums, or tiny red spots on the skin. Autoimmune destruction of red blood cells occurs in 4% to 7% of patients, leading to anemia and fatigue. Beyond blood cell problems, some people develop arthritis (about 3%), psoriasis, vitiligo, or less commonly, lupus or Sjögren’s syndrome. In some cases, autoimmune symptoms actually appear before the infections that eventually lead to a CVID diagnosis.
Cancer Risk
People with CVID face a higher risk of certain cancers. In a multicenter study of 250 patients, about 15% were diagnosed with cancer over the course of their follow-up. Non-Hodgkin lymphoma was the most common, affecting roughly 4.4% of patients. Gastric cancer (2%) and lung cancer (1.2%) were the next most frequent. Immune dysregulation more than doubled the odds of developing cancer, and prior use of immune-suppressing medications also raised the risk. This is why long-term monitoring, including periodic imaging and screening, is part of standard CVID care.
Treatment With Immunoglobulin Replacement
The cornerstone of CVID treatment is immunoglobulin replacement therapy, which provides the antibodies your body can’t make on its own. These antibodies are pooled from thousands of blood donors and given either through an IV or injected under the skin.
Intravenous infusions are typically given every three to four weeks at a hospital or infusion center, with each session lasting a few hours. Subcutaneous infusions offer more flexibility: you can learn to give them at home, either weekly or even daily in smaller doses. Some formulations allow you to maintain a three- to four-week schedule similar to IV treatment. The total monthly dose is roughly the same regardless of how it’s delivered. For people with lung damage from past infections, guidelines recommend maintaining higher antibody levels to slow further progression.
Most people tolerate immunoglobulin therapy well. Common side effects include headaches, fatigue, and mild reactions at the infusion or injection site. The therapy doesn’t cure CVID, but it dramatically reduces infection frequency and severity. Many patients describe it as life-changing, going from constant illness to a near-normal rate of infections.
Ongoing Monitoring
CVID is a lifelong condition that requires regular follow-up. Current guidelines recommend annual high-resolution CT scans of the lungs for patients with bronchiectasis, along with techniques to help clear mucus from the airways. Blood work to track antibody levels helps ensure replacement doses remain adequate.
A serious lung complication called granulomatous-lymphocytic interstitial lung disease can develop in some CVID patients, causing inflammation and granulomas (small clusters of immune cells) in the lung tissue. This condition requires more aggressive treatment with medications that suppress the overactive parts of the immune system. Screening for autoimmune problems, liver disease, and cancers is also part of routine long-term care, since these complications can emerge years or even decades after the initial diagnosis.